Epigenetic Associations with Estimated Glomerular Filtration Rate among Men with Human Immunodeficiency Virus Infection

Background: People living with human immunodeficiency virus (HIV) infection have higher risk for chronic kidney disease (CKD), defined by a reduced estimated glomerular filtration rate (eGFR). Previous studies have implicated epigenetic changes related to CKD; however, the mechanism of HIV-related CKD has not been thoroughly investigated. Methods: We conducted an epigenome-wide association study of eGFR among 567 HIV-positive and 117 HIV-negative male participants in the Veterans Aging Cohort Study to identify epigenetic signatures of kidney function. Results: By surveying more than 400 000 cytosine guanine dinucleotide (CpG) sites measured from peripheral blood mononuclear cells, we identified 15 sites that were significantly associated with eGFR (false discovery rate Q value < 0.05) among HIV-positive participants. The most significant CpG sites, located at MAD1L1, TSNARE1/BAI1, and LTV1, were all negatively associated with eGFR (cg06329547, P = 5.25 × 10^-9; cg23281907, P = 1.37 × 10^-8; cg18368637, P = 5.17 × 10^-8). We also replicated previously reported eGFR-associated CpG sites including cg17944885 (P = 2.5 × 10^-5) located between ZNF788 and ZNF20 on chromosome 19 in the pooled population. Conclusions: In this study we uncovered novel epigenetic associations with kidney function among people living with HIV and suggest potential epigenetic mechanisms linked with HIV-related CKD risk.